Renal transport and metabolism of low mol. wt. proteins, particularly peptide hormones such as parathyroid hormone and insulin, will be studied. The isolated perfused rat kidney will be used, an approach which permits the estimates of: (1) the concentration of proteins in glomerular filtrate, hence filtered loads and absorption rates; (2) the metabolic rate of absorbed proteins; (3) renal pathways of extraction; (4) contribution of the kidney to the plasma turnover of proteins. Using isolated perfused tubules of rabbit kidneys, kinetics and mechanisms of tubular protein transport are being investigated with particular emphasis on specificity and cell activity of transfer mechanisms. The central aim is to elucidate the role of the kidney in the turnover and regulation of plasma levels of low mol. wt. proteins and mechanisms by which this role is accomplished. Hopefully the results will also permit a better understanding of tubular proteinurias and of the alterations of plasma turnover and concentration of low mol. wt. proteins and peptides in renal failure. An additional part of this proposal is the study of the influence of changes in protein concentration on proximal tubular fluid reabsorption in the isolated rat kidney preparation. Combined with perfusion of proximal tubules at known rates, this preparation offers the advantage of separating the influences of tubular load from peritubular factors since both sides of the epithelium can be altered experimentally. The aim of the study is to make a quantitative assessment of the influence of physical forces (oncotic and hydrostatic) on proximal reabsorption. Hopefully, the study will provide information regarding the question of the influence of physical forces on the regulation of proximal tubular reabsorption in the mammalian kidney.